Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are implicated in the modulation of cough and nociception. TRPA1 and TRPV1 have important roles in the sensation of pain, temperature, inflammation and cough in animals and man. TRPV1 is activated by warm temperatures (above 43° C.), protons and noxious chemicals such as capsaicin and resiniferatoxin. TRPA1 is activated by cold temperatures (below 17° C.), and a wide range of irritating and pain stimulating chemicals such as acrolein (found in smoke), formalin, mustard oil and allicin (found in onions and garlic) as well as cinnamaldehyde (extracted from cinnamon). Occasionally, TRPA1 and/or TRPV1 respond to compounds which are potentially beneficial, possibly creating a sense of irritation, burning, or pain that can discourage the use of beneficial products.
Functional TRP channels have been thought to be tetramers, possibly either homo-tetramers or even hetero-tetramers. In vivo, TRPA1 is known to be expressed in the same sensory neurons as TRPV1 and pharmacological interaction between the two receptors has been established. Direct interaction resulting in hetero-tetramers between these two channels has been demonstrated using transient co-expression of the two receptors in CHO cells. Nonetheless, in vitro models for irritation, burning, and pain have tended to focus on TRPA1 or TRPV1 rather than TRPA1V1.
There remains a need to modify unpleasant sensations associated with beneficial products.